DESCRIPTION: Naked DNA vaccines have factors, such as ease of preparation, exposure to multiple antigens, and safety that make them attractive candidates for protection from HIV infection. This proposal is designed to develop a model DNA vaccine based on constructs that would encode all or nearly all of the SIV proteins, but would not be infectious because of multiple mutations including deletion of the packaging site and mutations in nucleocapsid. The applicant will test the immune responses engendered by the candidate DNA vaccine in macaques, and will test the efficacy of the vaccine after mucosal SIV challenge.